The Pitmen secured a 4-2 win in the Turkish capital, positioning themselves advantageously for the return leg next Thursday in Krakow. They took the lead within just seven minutes through Alisson, as the Brazilian winger outmaneuvered several defenders before sending Mert Gunok the wrong way.
Eguinaldo added a second just before the half-hour mark, giving the Ukrainian giants a two-goal cushion. A few minutes before halftime, Tammy Abraham scored from the penalty spot for the home team.
Arda Turan's squad maintained their solid performance with a series of 51 passes that led to Kevin scoring their third. The former Palmeiras player netted a fourth in stoppage time after Joao Mario had scored a second ten minutes earlier.
Shakhtar, who now hold a 9-1-0 record against Turkish teams, have scored 10 goals in Europa League qualifying this summer, more than any other team.
In other matches, Eredivisie team Utrecht overcame an early setback to win 3-1 against Sheriff Tiraspol. Souffian El Karouani set up Victor Jensen and Nick Viergever to give his team the lead, before Adrian Blake added a third 20 minutes from the end.
There were two matches that ended without goals. The UEL's consistent team, Sporting Braga, were held in Bulgaria against Levski Sofia, marking the first time since the competition's current format began that the Portuguese team was unable to score in a qualifier away from home.
The other scoreless match took place in Switzerland, where CFR Cluj's Karlo Muhar failed to convert a penalty just 11 minutes in against Lugano. While the home team dominated possession, they failed to convert any of their 11 attempts into a goal.
Anderlecht were the only other team to secure a win that night, courtesy of a Kasper Dolberg goal ten minutes before halftime. That was sufficient for them to achieve a narrow 1-0 victory over Hacken.
Doguhan Simsirequalized Jamie McGrath's opener for Hibernian as they finished 1-1 in Denmark against FC Midtjylland. Regarding Banik Ostrava, they twice took the lead against Legia Warsaw, but were equalized twice in their 2-2 draw. Michal Frydrych thought he had netted his second of the match at the end, but it was disallowed for offside.
In Cyprus, Celje and AEK Larnaca could not be distinguished, as the match concluded 1-1. Both teams scored via penalties, with the Slovenians leveling eight minutes after the restart.
All eight return legs are scheduled for next Thursday, with the winners advancing to August's third qualifying round. Joining them will be Wolfsberger, Fredrikstad, and PAOK, along with the 15 teams that lost in the Champions League second qualifying round.