Timo Werner from the penalty spot gave RB Leipzig a 1-0 victory at Tottenham Hotspur, while Atalanta defeated Valencia 4-1 in the first leg of their last 16 Champions League matches on Wednesday.
Werner converted in the 58th minute as the visiting Bundesliga side dominated an injury-hit Tottenham side.
Champions League debutants Atalanta were meanwhile always in control over Valencia in Milan. Hans Hateboer scored two and Josip Ilicic and Remo Freuler were also on target before Denis Cheryshev gave Valencia a glimmer of hope for the return leg on March 10.
In London, Tottenham had to thank keeper and captain Hugo Lloris for keeping them level in the first half.
The France keeper deflected an Angelino shot onto the post and saved from Werner in the opening two minutes in a fast start by the Bundesliga side, playing for the first time in the competition's knock-out stage.
Spurs had a chance when Steven Bergwijn's shot was saved by Peter Gulacsi, but Patrik Schick headed just wide from a corner and Lloris was again in action to block a Werner effort.
Nineteen-year-old Wales international Ethan Ampadu, on loan from Chelsea, replaced suspended Dayot Upamecano in central defence for Julian Nagelsmann's side.
But Spurs, with only Lucas Moura up front in the absence on injured Harry Kane and Son Heung Min, rarely threatened the Leipzig defence in the first 45 minutes.
Moura immediately tested Gulacsi shortly after the break but it was Leipzig who broke the deadlock when Werner beat Lloris from the penalty spot in the 58th minute following a clumsy challenge by Ben Davies on Konrad Laimer.
Lloris prevented Spurs from going further behind when he saved from Schick, while at the other end Gulacsi diverted a Giovani Lo Celso free-kick onto the outside of the post. Moura headed over the bar in a late chance in a spell of belated pressure from Jose Mourinho's side.
"We didn't allow much at the back and created a lot of chances up front," Werner told Sky Sports. "We were a bit surprised we had so much of the ball."
Lloris told BT Sport: "I want to stay positive especially after what we saw in the last 20 minutes. There is a second leg and we have a chance. It's not the best result we could get."
He added: "There is a lot of quality in Leipzig and they showed it today. Because of all the circumstances against us in the past few weeks and months we have to stay positive."
The evening's other tie was played at Milan's San Siro, because Atalanta's home ground in Bergamo does not meet UEFA requirements.
Valencia were back at the stadium where they lost the 2001 final to Bayern Munich, but it was an unhappy trip for the Spanish side.
Hateboer finished from close range in the 16th minute and Ilicic fired a second from the edge of the area three minutes before the break to put Atalanta in control.
A third came in the 57th minute when Freuler curled the ball into the net from the edge of the area, and Hateboar got his second in the 62nd before substitute Cheryshev found the net for the visitors four minutes later.
Tuesday's first two first-leg ties saw Atletico Madrid beat defending champions Liverpool, and Borussia Dortmund defeat Paris Saint-Germain 2-1.