Maldonado, starting from pole position, held his nerve as he withstood the challenge of Ferrari's Spanish driver to take the 66-lap race at the Catalunya Circuit by 3.1 seconds and give F1 its fifth different race winner of a so far unpredictable season.
Maldonado's victory provided icing on the cake for Frank Williams as the team celebrated its longtime team principal's 70th birthday this weekend. Williams' celebration speech, however, was cut short after a fire broke out after the race, with the longtime team principal having to be led away from the garage when the fire broke out.
One person was airlifted to hospital with severe burn wounds while five more were treated at local hospital for smoke inhalation. Ten of the injured were treated for smoke inhalation at the track before being released. Caterham said four of its own team members were among those injured as the fire spread to neighbouring team boxes.
Maldonado become the sport's first Venezuelan winner, while Williams' 114th triumph was its first since the 2004 Brazilian GP.
"It's a wonderful day for me and the team. An unforgettable race," said Maldonado, who was hoisted onto the shoulders of Alonso and Kimi Raikkonen before being doused in champagne on his first visit to the podium. "It was a tough race, with the strategy and a couple of laps we were struggling. But the car was so competitive from the first lap."
Raikkonen made up nearly 20 seconds over the final stretch to finish 3.8 seconds behind Maldonado in third, ahead of Lotus teammate Romain Grosjean.
Kamui Kobayashi of Sauber was fifth, ahead of two-time defending F1 champion Sebastian Vettel, who charged past Nico Rosberg's Mercedes to take sixth and maintain a share of the overall F1 points lead.
The Red Bull driver, who was given a drive-through penalty during the race, shares 61 points at the top of the driver standings with Alonso through five races. It is F1's most varied start since 1983, when five different drivers also opened the season with victories.
Hamilton is third with 53 points, while Raikkonen has 49, one better than Red Bull driver Mark Webber, who finished 11th. The top seven drivers are separated by less than the 25 points awarded to the winner of each race, and Grosjean trails the top two by 26 points.
"These tires are contributing to an extraordinary season," McLaren team principal Martin Whitmarsh said. "Anyone who makes predictions in the sport right now would be nuts."
Mercedes driver Nico Rosberg was seventh and Lewis Hamilton, demoted from pole to last place in the 24-car field because of a rule breach, finished eighth for McLaren.
Hamilton finished ahead of teammate Jenson Button with Force India driver Nico Hulkenberg taking the last two points in 10th.
Alonso provided home fans with a steely start as the two-time champion kept his inside line, under pressure from Maldonado. The Spaniard led around the first corner with Raikkonen moving ahead of Grosjean to sit third.
Hamilton, who set the fastest lap in Saturday's qualifying but failed to retain enough fuel in his tank to get back into the pits, overcame a poor first stop when his crew failed to clear a tire quickly to stay in the points. He moved as high as fifth after the second round of stops, when Maldonado took over the lead from Alonso, with Raikkonen still ahead of Grosjean.
"It was the best I could do," said Hamilton, who felt he had a point to prove. "I was one of the only ones to do a two-stop strategy and people always commenting how aggressive my driving style is, so I hope today I could prove them wrong."
Maldonado lost time on his third stop but managed to eventually get past Raikkonen to open up a gap on Alonso, who passed the Finn one lap later to stay on Maldonado's back.
"It was a fantastic start. We took the momentum there and led the race for the first start but Williams anticipated (our pit) stop and got in front," said Alonso, who finished runner-up for the fourth time. "We tried a couple of times to get in front but it wasn't possible."
The 27-year-old Maldonado drove with confidence down the final stretch despite Alonso, whose lone victory here was in 2006, bearing down on him.
"There was some moments where he was so close but I managed the gap," Maldonado said.
Michael Schumacher bowed out after running into the back of Senna on lap 14, the German driver's terrible season getting worse as he failed to finish for the third time while also knocking his Brazilian rival out of the race.
Hamilton stayed third in the driver standings ahead of Raikkonen going into the Monaco GP on May 27.
"It's a great opportunity for us to be strong again," Maldonado said. "Consistency will be the most important thing this championship."
Paul Logothetis can be reached at: www.twitter.com/PaulLogoAP