Josh Harrison hit his third home run and Ike Davis also had two hits.
The Nationals jumped on Liriano for two runs in the first inning. Span led off with a double and later scored on a wild pitch. Desmond followed with his first RBI single.
Washington doubled its lead to 4-0 in the fifth when Rendon hit a run-scoring triple and scored on another wild pitch by Liriano, who won 16 games last season.
"I thought he had sequences of all three pitches in some spots," Pirates manager Clint Hurdle said of Liriano. "The consistency, drawn out over the five innings, was not there."
Harrison led off the sixth inning with his home run, a drive into the visitors' bullpen in center field, but the Nationals got the run back in the seventh on a second run-scoring single by Desmond.
Davis singled in a run in the eighth to draw the Pirates within 5-2.
Washington is 21-1 when scoring four runs or more and 4-21 when it doesn't.
NOTES: The Pirates plan to recall RHP Brandon Cumpton (0-1 4.26) from Triple-A Indianapolis on Monday to start against Mets RHP Jacob DeGrom (0-2, 2.77) at New York. Cumpton, a rookie who made two starts for Pittsburgh earlier this season, will take the rotation spot of LHP Wandy Rodriguez, who was designated for assignment Thursday. ... Washington activated 1B Adam LaRoche from the 15-day disabled list before the game and he batted cleanup. LaRoche had been out since May 10 with a strained right quadriceps. ... Nationals 2B Danny Espinosa got a day off after going 4 for 36 (.111) with 16 strikeouts in his previous 10 games. ... Washington hosts the Miami Marlins on Monday with RHP Tanner Roark (3-2, 3.42) facing RHP Nathan Eovaldi (3-2, 3.41).