Alexander Zverev got the better of older brother Mischa at the Citi Open in Washington on Thursday, winning their first meeting at an ATP Tour event 6-3, 7-5.
World number three and top seed Alexander, 21, broke Mischa, 30, three times en route to a victory that sets up a quarter-final with seventh seed Kei Nishikori, who dispatched Canadian teenager Denis Shapovalov 7-6(1), 6-3.
Despite the loss, Mischa said it was a match he would always remember.
"After the coin toss I had tears in my eyes because it felt so special," he added.
"I wondered what are my parents thinking right now. I needed a few seconds to bite my tongue and focus."
The younger Zverev said he hoped to see his brother across the net again in the future.
"I hope this is not the last time. I hope we play a final one day," said Alexander, the tournament's defending champion.
Earlier in the day, second seed John Isner was upset by fellow American Noah Rubin 6-4, 7-6(6) in the second round.
Isner, last month's Atlanta Open champion, appeared fatigued during the match, perhaps owing to a busy July where he played 10 matches consisting of 34 sets and 403 total games.
The win over world number nine Isner was the 22-year-old Rubin's first over a top 10 opponent.
Due to rain delays earlier in the tournament, however, Rubin had to play 20-year-old Russian Andrey Rublev later on Thursday where he fell 6-3, 6-2.
Stefanos Tsitsipas of Greece, the 10th seed, capitalised on a strong service game that included eight aces to earn a 6-3, 6-4 win over Australian James Duckworth.
Tsitsipas will face third seed David Goffin in the quarter-finals after the Belgian beat American Frances Tiafoe 6-0, 6-3.
Venus Williams tops Watson at Silicon Valley Classic
Venus Williams found her winning form late and charged to a 6-4, 4-6, 6-0 win over Britain's Heather Watson at the Silicon Valley Classic on Thursday to punch her ticket to the quarter-finals.
The typically reserved 38-year-old American broke Watson six times and showed rare flashes of emotion after critical points in the two-hour affair, pumping her fist and shouting.
"I'm calm. I can't help how I am," the third-seeded Williams said when asked if she would continue with the new on-court demeanor.
"But I'm definitely fired up inside."
Next up for the seven-time Grand Slam champion is a showdown with Maria Sakkari of Greece, who strolled to a 6-0, 6-1 win over Hungarian Timea Babos earlier in the day.
"I've got to play my best again," said Williams, who has gotten the better of the 23-year-old Sakkari in their two prior meetings.
"It's never easy. I've got to earn it just like tonight so I'll be doing the same thing tomorrow."
Williams is the highest remaining seed in the tournament after defending champion Madison Keys withdrew from the tournament on Thursday prior to her second-round match against Ajla Tomljanovic due to pain in her right wrist.
The hard-hitting 23-year-old, runner-up at last year's U.S. Open where she lost to fellow American Sloane Stephens, is ranked 12 in the world and was the second seed in San Jose.
"I am really sorry to have to pull out of the Mubadala Silicon Valley Classic," Keys said. "I have been feeling pain in my wrist over the last couple of days and felt worse today.
Keys was replaced in the draw by Polish lucky loser Magdalena French who fell 6-4, 3-6, 6-3 to the Australian Tomljanovic to set up a quarter-finals battle with Romanian Mihaela Buzarnescu on Friday.
On Wednesday top-seeded Spaniard Garbine Muguruza withdrew due to a right arm injury.
Paire fined $16,500 for Washington meltdown
French player Benoit Paire has been fined $16,500 after a racket-smashing meltdown during his first-round defeat by Marcos Baghdatis at the Washington Open this week.
Paire, known for his volatile temperament, smashed three rackets and kicked a courtside bench and was booed off the court after appearing to give up on match point down.
The 29-year-old initially lost his cool when dropping serve to trail 5-2 in the final set of his 6-3, 3-6, 6-2 defeat.
After falling, he smashed his racket over and over into the court, then took another one from his bag and destroyed that. Another frame bit the dust at the end of the contest.
Paire was sanctioned for 'audible obscenity, unsportsmanlike conduct and a lack of giving best effort'.
"Yes, yes it's true I got upset yesterday," he wrote on Instagram.
The ATP fine was more than double the appearance money he made at the tournament.