The second round tie was fiercely contested, and despite the emphatic scoreline it needed extra-time to separate the two sides, after a dramatic end to the ninety minutes.
There was a fanatic pace and intensity to the game from the off and early appeals from Sussex for a penalty were turned away after striker Alfie Rogers went down in the box.
Soon after, a beautifully whipped in Sussex corner fell to Essa Janneh in the box, but his effort cannoned back off the crossbar.
At the other end Berks & Bucks appeared to have taken the lead through left winger Aiden Higgs, but the goal was ruled out after a lengthy chat between the officials.
The second-half started at much the same pace as the first, with the first clear cut chance of the half falling to Berks & Bucks Ewan Lynch, but Tom McAlpine in the Sussex goal stood strong to make the save.
Sussex’s first attacking threat of the second-half came after centre-back Rob Malila made a strong tackle and drove forward with the ball before feeding Rob Deda, but he could only blast wide.
Defensively Fintan Walsh was having a fine game for Sussex, seemingly finding himself in the right place at the right time to intercept and clear Berks & Bucks advances.
Into the final ten minutes and the match look destined for extra-time with neither side able to break the deadlock.
But then, Sussex captain Rogers burst through the Berks & Bucks backline before being felled in the box giving the referee no option but to point to the spot.
Rogers dusted himself down and took the penalty only to see the Berks & Bucks goalkeeper make a fine save down to his left hand side to keep the score level.
However, buoyed by the penalty save, Berks & Bucks went immediately on the attack and a deep cross to the back post found Aiden Higgs unmarked and his header looped over McAlpine and into the net.
That goal looked to have won the game late on for Berks & Bucks but more drama was in store.
With little time remaining Sussex broke forward from the restart and, eager to make amends for his penalty miss, Rogers played a lovely weighted ball into strike partner Tyler Pearson, who confidently swept the ball home to draw the game level again.
Sussex created the first opportunity of extra-time as Pearson found space, but his shot was charged down by Berks & Bucks defenders.
Seconds later Berks & Bucks restored their lead, right-back Geoff Kibaki was the first to react and fire in the rebound after McAlpine could only parry an opportunist effort into his path.
The attacking full-back Kibaki was up-field again moments later, this time a good run and a wonderfully delivered cross set up an opportunity for Nathan Hodge, but the latter could only direct his header wide of the post.
Into the second-half of extra time and Sussex had no choice but to push forward in search of a route back into the game. This left them susceptible to the counter-attack and Berks & Bucks exploited this.
Substitute Bhumlemi Bhembe added a third for Berks & Bucks with a neat finish into the bottom corner.
Bhembe then got his second and Berks & Bucks fourth minutes later, a fantastic weaving run past several Sussex defenders created the opportunity and he took it emphatically.
There was still time for Hodge to receive his marching orders after picking up a needless second yellow card for dissent, and Alex Rice to add extra gloss to the scoreline with a well taken finish in the top corner past McAlpine to seal the 5-1 victory.
Following the defeat Sussex County FA Assistant Manager, Ian Browne said: “I’m disappointed with the result; however, there were some good individual performances on display particularly at the back.
“I couldn’t fault the team’s desire to do well, but you know it's not going to be your day when you miss a penalty and they go straight down the other end and score!”
(A selection of photos from the match can be found on Facebook - further photos via Simon Roe Photography)
Stats: (Berks & Bucks-Sussex)
Goals: 5-1; Shots: 10-5; Shots-on-target: 7-3; Corners: 6-5; Fouls: 14-10; Offside: 0-2; Yellow cards: 1-3; Red cards: 1-0.
Sussex: McAlpine, Williamson (Addy 105), Proto-Gates, Janneh, Malila, Walsh, Waters (Colbran 55), Plummer (Brown 59), Rogers, Deda, Pearson.
Match report by Jordan O’Sullivan