The curly-topped 24-year-old Brazilian Luiz curled the ball around the German defence and into the far corner of the net after a superb 67th minute build-up involving Ashley Cole and Fernando Torres to put Chelsea on the road to a hard-fought victory in a tough group opener.
Mata made it 2-0 in the third minute of stoppage-time.
A minute before Luiz scored, Leverkusen almost took the lead when former Chelsea favourite Michael Ballack advanced on goal with only Petr Cech to beat, but the Czech keeper blocked his former team-mate's shot.
Both teams had the ball in the net inside the opening four minutes, but both goals were disallowed by the officials.
Chelsea manager Andre Villas-Boas, in charge of his first Champions League match, left veterans John Terry and Frank Lampard out of the starting line-up, and his gamble paid off as a youthful looking Chelsea team picked up three valuable points.
Leverkusen thought they had taken the lead after three minutes when Simon Rolfes headed home but French referee Stephane Lannoy ruled Leverkusen's players guilty of pushing from the free-kick that led to the disallowed effort.
Television replays failed to show any clear infringements however.
Less than a minute later Chelsea thought they had scored when Torres flicked the ball into the net but Raul Mereiles, who attempted to back-heel the ball home, was ruled offside and the goal ruled out.
Torres, who had only scored once for Chelsea in 22 previous matches since his record 50.0 million pounds move from Liverpool in January, worked tirelessly in attack alongside the impressive Daniel Sturridge and went close to scoring with an acrobatic overhead-kick in the first half which went just over the bar.
Although he failed to score, he played an important part in both goals and while his manager did not praise him individually afterwards, he did praise his team's performance.
"It was a difficult game for us but it was a fair result with Chelsea winning. There was excellent work from everybody, an excellent effort, tremendous amount of workrate and possession and shots on goal and I am very happy with everybody," he told Sky Sports afterwards.
Leverkusen defended well, however, and created enough chances of their own with Cech also forced into making good saves from Lars Bender and Andre Schurrle in the second half.
