Second-year guard Bradley Beal scored a team-high 25 points, Trevor Ariza made all six of his three-pointer attempts for 22 and the Wizards drew first blood on the road in the best-of-seven series.
Washington turned heads when they beat the Chicago Bulls in just five games in the first round of the post-season and are playing in the second round for the first time since 2005.
"We feel like we're capable of winning when we play our style of basketball," Ariza told reporters.
"We hadn't won (in Indiana) in a while, why wouldn't this be the best time to come in and get a win?" The Pacers, needed the full seven games to survive and advance against eighth seed Atlanta in the opening round also held form after they, again suffered from inconsistency.
Paul George, who led the charge with 30 points in Indiana's Game Seven triumph Saturday, was off his game against the Wizards, scoring 18 points on 4-for-17 shooting.
George Hill also tallied 18 points for the Pacers but they could not catch up after Washington's hot start, the Wizards scoring the game's first eight points and leading 28-15 after the first quarter.
Washington, who stay in Indiana for Game Two on Wednesday, particularly pounded the Pacers inside where they won the rebound count 53-36.
Center Marcin Gortat finished with 12 points and 15 rebounds, while Drew Gooden contributed 12 and 13 rebounds off the bench for the Wizards.
Conversely, Indiana big man Roy Hibbert, who has been in disappointing form in the post-season, did not record a point or rebound in 18 minutes.
"We can't put ourselves in these corners. We should learn from the first series," George said.
"It's going to be a tough series for us, but we can't allow ourselves to be put in these holes."
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Chris Paul missed just two shots in a stunning 32-point display as the Los Angeles Clippers blasted the Oklahoma City Thunder 122-105 to seize a Game One victory in their Western Conference semi-final series.
Paul made his first eight three-pointers, a career-best total, and finished 12-for-14 from the field with 10 assists as Los Angeles enjoyed a surprisingly dominant road win to open the best-of-seven series.
"It was just one of those nights. This will definitely go down in the history books for me," Paul said.
With the victory, the Clippers continued to distance themselves from the cloud of controversy that hovered above a first round series overshadowed by owner Donald Sterling's racist comments that led to a life ban from the NBA.
The Clippers were expected to ease past Golden State but despite the unwanted distraction created by Sterling's remarks, Los Angeles held on to edge the sixth-seeded Warriors in a hard-fought series that went the distance.
The Thunder also waded through a seven-game struggle of their own against Memphis but appeared ill-prepared for a free-scoring Los Angeles team, despite 29 points from Russell Westbrook and 25 from Kevin Durant.
Paul showed his hand early, pouring in five three-pointers in the first quarter alone to lead the road team to a 39-25 advantage at the break.
The Clippers continued to build on their momentum as the Thunder appeared powerless to slow them down with Los Angeles leading by as much as 29 points late in the fourth quarter.
All Star Blake Griffin finished with 23 points and Jamal Crawford added 17 off the bench in the winning effort.
Oklahoma City Thunder guard Thabo Sefolosha, regarded as a defensive specialist, rejoined the starting line-up after being benched for the past two games but his presence had almost no effect on the Clippers' offense.
"We have to be more physical with them, and make them feel us a little bit more," Durant said.
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