However, the Cubs' bats were quick to pick up the slack as Chicago held on for an 8-7 victory over the San Diego Padres.
The victory was eighth straight for the Cubs, who ran their major-league-best record to 25-6. The Padres (13-20) took their third consecutive loss.
"We had to kind of invent ways to get guys out tonight," Lester said. "(I) didn't really have anything, curveball stunk, cutter was hit or miss, so we really (just) had a fastball."
The Cubs left-hander allowed a season-high-tying three runs on four hits over six innings in his seventh start. Lester (4-1) struck out four and walked one in a 105-pitch effort.
"Jon didn't have his best thing going on today, but he fought through six, which we needed," Cubs manager Joe Maddon said. "But we played well offensively. ... When you're able to give up seven and win, that's a pretty good thing."
The Cubs pounded out 10 hits as Ben Zobrist went 4-for-4 and scored three times in the belated series opener.
Padres starter Cesar Vargas (0-2) lasted just four innings. He gave up six runs on 10 hits, walked three and struck out just one while throwing 92 pitches.
Leading 6-3 in the seventh, the Cubs added two runs they would ultimately need.
With runners on second and third, Addison Russell's one-out triple to right off reliever Luis Perdomo brought in Anthony Rizzo and Zobrist for an 8-3 lead.
San Diego replied with four runs in the eighth after loading the bases on Chicago reliever Justin Grimm with one out.
Pinch hitter Alex Dickerson launched his first career home run -- a grand slam -- to right off right-hander Adam Warren to cut the deficit to 8-7.
"It's really a historic place, very big spot in baseball," Dickerson said. "It's really special to make my mark in my career at a place like this."
Cubs reliever Hector Rondon preserved the win with a one-two-three ninth -- including two strikeouts -- to earn his seventh save.
"At the end of the night, how about Ronnie (Rondon)," Maddon said. "He went out there like a big league closer and did his job. It was outstanding to watch."
The Padres finished with eight hits, including two home runs, on a cool, humid night.
"I thought the offense was great today," Padres manager Andy Green said. "We swung the bats really well. Guys kept fighting, kept fighting. We had multiple chances and cashed in a number of times. We put seven runs on the board against a tough pitching staff."
The Cubs took a 1-0 lead in the second as Zobrist singled with one out, reached second base on a Javier Baez infield hit and scored as Russell launched a double into the right field corner.
Russell was tagged out after attempting to take third while Baez also was at the base. Russell rushed back to second base, where he caught.
The Padres had runners at first and second after a walk and a hit batter with two out in the third, but Lester struck out Wil Myers looking to end a threat.
The Cubs hit Vargas for four runs in the bottom of the inning.
San Diego moved infielders to the right for Jason Heyward, leaving a gaping opening along the third base line. Heyward lined a base hit right where third baseman Brett Wallace would have been, advancing Dexter Fowler to second.
Both came home on Kris Bryant's double to deep left for a 3-0 lead. Bryant scored on Zobrist's RBI single for a 4-0 advantage.
Baez doubled, Russell was intentionally walked to load the bases with one out and Ross sent a deep fly to right to score Zobrist for a 5-0 lead.
The Padres got one run back in the fourth when Melvin Upton Jr. had the first hit off Lester -- a two-out solo home run to left.
Zobrist made it 6-1 in the fourth with his third hit and second RBI of the night, bringing in Heyward from third with two outs.
Tuesday's game kicked off the three-game series after Monday's game was rained out. The postponed game will be played as part of a split doubleheader Wednesday.
NOTES: The Padres claimed LHP Keith Hessler off waivers from the Diamondbacks. He was 0-1 with an 8.22 ERA in 20 appearances spanning two seasons for Arizona, including two in relief this year for three innings and no record or saves. ... Monday's rainout was the Padres' first on the road since early in the 2014 season at Cleveland and Cincinnati. ... Wednesday's scheduled split doubleheader starts at 1:05 p.m. ET and ends with an 8:05 p.m. ET nightcap. ... Padres RHP Colin Rea (3-1, 3.82 ERA) goes against Cubs RHP Kyle Hendricks (2-2, 3.10) in Game 1. San Diego LHP Drew Pomeranz (3-3, 2.12) faces Chicago RHP John Lackey (4-1, 4.02) in the evening. ... Cubs C Miguel Montero, who is on the 15-day disabled list, reported to Triple-A Iowa for a rehab assignment as he recovers from a lower back tightness. "Let him go play and see how he feels," Cubs manager Joe Maddon said. ... Monday's rainout was the Cubs' third of the season, all within the past 10 scheduled home dates.