Tipirneni conceded the race Wednesday after initially saying the outstanding votes made it too close to call.
Lesko has a 52.6 percent to 47.4 percent lead over Tiperneni, or 91,390 votes to 82,316 — an Republican advantage of 9,072 votes, with 100 percent of precincts reporting, according to the Arizona secretary of state's office.
That margin may concern Republicans. President Donald Trump carried the district in the conservative Western Phoenix suburbs by 21 percentage points, and its previous occupant, Trent Franks, a Republican, ran unopposed.
House Speaker Paul Ryan, R-Wis., congratulated Lesko on the victory, saying she ran a smart campaign "and focused in on the issues that voters cared about, like having more take-home pay, fewer regulations, and a secure border."
"Her victory proves that Republicans have a positive record to run on this fall and we need to spend the next seven months aggressively selling our message to the American people," Ryan added.
But some Democratic activists saw the results quite differently.
"This is a race that was never supposed to be competitive," Maria Urbina, national political director for the Indivisible Project, said in a statement.
National Democrats largely stayed away from the race, with strategists downplaying expectations in a district made up largely of older, white voters. It includes in the large Sun City retirement community.
Most voters were able to submit their ballots by mail, which was thought to favor Republicans by limiting the effect Democrats' enthusiasm advantage would have on turnout.
Democrats have consistently improved on their past performances in special elections across the country since Trump's election, even when they lost, and Tuesday's race continued that trend.
Results like Tuesday's have Democrats hoping they're on track for big victories in November's midterms.
"It should terrify vulnerable Republicans that their party had to run a desperate rescue mission to hold on to this deep red seat in Arizona," said Jacob Peters, a spokesperson for the Democratic Congressional Campaign committee. "Republicans shouldn’t have had to spend a dime to hold this district."
Lesko and Tipirneni are poised for an almost immediate rematch in November, because the special election was called only to fill the rest of Frank's term.
Tipirneni has already said she will run, and Democrats think she has a better chance then.