NOTE: This spoiler was sent in by Steve H.
"Curious George" opens with George himself frolicking in the jungle, playing with his animal friends. You can see right away that George is quite the mischief maker.
Then we're introduced to The Man in the Yellow Hat (Will Ferrell), who's real name is Ted. Ted is a bit of a bumbling tour guide at a museum. He's giving a tour to Maggie's (Drew Barrymore) class and it quickly becomes clear that Maggie regularly visits the museum for tours because she's smitten with Ted.
After this particular tour, Ted meets up with his boss, Mr. Bloomsberry (Dick Van Dyke) and Bloomsberry's son, Junior (David Cross). Turns out the museum is in dire financial straits and will likely close down very soon unless the situation improves. Junior's excited about this because if the museum does close, he'll be able to build a brand new parking garage in its place and make a mint. But Ted's life is the museum and he wants it to stay in business. So Ted offers to go into the deepest jungle to find the lost Shrine of Zagawa, a fabled 40 ft. red monkey statue that Bloomsberry has always wanted for his collection. Ted figures this amazing artifact will be the key to bringing in the crowds and the money to keep the museum open. Bloomsberry heartily agrees, but Junior sees this as the monkey wrench in his plans, so he sabotages the treasure hunt by destroying a critical part of the Zagawa map, unbeknownst to Ted.
To prep for the mission, Ted figures he needs some good jungle wear, so he stops by a Banana Republic-y shop where a couple of clerks are sorting through boxes and boxes of all-yellow safari clothes they just got stuck with. Ted being the somewhat naïve guy that he is, buys into their sales pitch when they claim that "yellow is the new khaki", and snaps up all of the outfits for his trip.
Ted goes off on his mission into the jungle. In nearby trees there, George happens to be happily munching on a banana. The jungle grass Ted is walking through is so tall, the only part of Ted George can see is the big banana-shaped yellow hat. Hungry for that giant banana, George scampers off to get it. This is where Ted and "that little monkey" meet for the first time (Ted doesn't give George his proper name until about 2/3rds of the way into the story upon Maggie's class' insistence). After a quick game of hide-and-seek inside the yellow hat, George realizes he likes playing with Ted and wants to hang around him. But Ted's on his mission and doesn't want to play any more, so he keeps trying to shoo George away.
The mission continues, but since the map was partially destroyed, Ted cannot go any further than a little stone altar where Ted discovers only a useless, miniature version (about 4" instead of 40 feet) of the Shrine of Zagawa. Crushed by his findings (or lack thereof), Ted takes a picture of the doohickey with his cell phone and sends it off to Bloomsberry so he can share the bad news. Unfortunately, Bloomsberry misinterprets what he sees in the photo. Ted snapped the picture from a lower perspective which made it look like a giant statue when compared to the trees far off in the background. Bloomsberry thinks Ted has found THE Shrine and excitedly goes off to make plans for its arrival at the museum before Ted has a chance to convince Bloomsberry otherwise. Ted then gives up on his mission and heads back on the cargo ship to the Big City. What Ted doesn't realize is that George has followed him and stowed away on the ship.
Back in the Big City, Ted heads on home. Along the way he is startled to realize that Bloomsberry has gone to town in promoting the grand arrival of the Shrine of Zagawa. There are banners and posters everywhere in the streets celebrating the opening of the exhibit. Looking at the tiny statue in his hand, Ted realizes he's sunk. Meanwhile, George somehow keeps pace with Ted through the streets, following him all the way back to Ted's apartment building. Unfortunately, more trouble begins to brew when the building's hulking doorman, Ivan, sniffs out the scent of a pet (i.e. George) through the building's air ducts. With his powerful sniffer, Ivan eventually traces the smell to Ted's apartment. The building has a "no pets" policy and there is no way Ivan is going to let any tenant get away with it.
While that hunt is on, Ted is shocked/happily surprised to see that George has followed him all the way from the jungle, arriving smack dab in the middle of the apartment. But before they can do anything about this, Ivan appears at the doorway, demanding to see what pet Ted has stashed away. George obliviously begins to explore the apartment and the rest of the floor in the building, out of sight from Ivan, looking for more fun and excitement. He quickly comes across the apartment of Ted's neighbor, a diva-like opera singer (Joan Plowright). While the singer is in her bath, George begins to play with the rainbow-colored selection of paints sitting in the dining room, which were waiting to be used to paint the walls. George's artistry gets many colorful drawings on the wall and lots of paint in the bath. Soon enough, Ivan catches up with the two here and evicts Ted.
So Ted and George are out on the street with no home and no solution to the museum problem. While Ted searches for ideas, George continues to make mischief. George knocks over a dinosaur statue (during a Shrine press conference Junior kicked off in an attempt to discredit Ted and his "discovery"). George puts fireflies in his mouth. George grabs a giant bunch of helium-filled balloons and leads Ted on a chase above the city.
Nearly ready to pack it all in after all this, Ted encounters Clovis (Eugene Levy), the museum's resident inventor. While poking around Clovis' laboratory, George accidentally invents a 3D projector, a machine that takes small objects and seemingly increases their size a hundred-fold. Recognizing how this could help with the mini-Shrine problem, Ted puts the machine in his truck and drives it over to where the exhibit will be held. Along the way, George monkeys with the machine and winds up casting a gigantic 40-ft. image of himself into the streets of the Big City. Citizens walking about those streets are astonished to see this King Kong-sized ape playing among the skyscrapers.
At the museum, the machine is set up and works wonderfully, projecting a perfect image of the Zagawa Shrine right where it needs to be until Junior sabotages the device by pouring coffee on it. He frames George in the process. Ted becomes furious at George for ruining this last chance to save the museum. In fact, he's so mad, he does nothing to stop Animal Control from coming along and snatching up George to deport him back to the jungle.
But Ted soon comes to his senses and decides to go rescue George. Ted races to the cargo ship that George has been placed upon and finds poor, little George locked up in a cage in the storage area. Ted lets George out shortly before discovering that the mini-shrine still in Ted's possession holds more than meets the eye. It turns out that when held up to the light, the mini-shrine casts on the wall a whole, intact map of where the real Shrine of Zagawa lies. It's that same jungle this cargo ship is headed to, so Ted and George sit tight awaiting their arrival. In a quick succession of events, we see that Ted discovers the real shrine after all and sends it back to the Big City, promptly placing it on display. The exhibit is a massive hit drawing in big crowds and big bucks, saving the museum.
Junior gets put it his place by having all his schemes thwarted. His role in the story ends as the opera singer from the apartment building comes to see the Shrine exhibit and asks Junior to park her car in the new very successful parking lot she just opened up down the street.
Ted realizes he's been spending too much time with the museum and needs to realign some of his priorities, especially raising those involving getting together with Maggie.
Bloomsberry, in appreciation, opens up a new wing of the museum dedicated to kid activities, which are activities that were inspired by George's antics. The movie ends as we find George getting on board a fully-fueled rocket ship from the Space section of the museum, hitting the ignition button just as Ted gets in.
The two fly off into space for their next big adventure.