The Cornwall/Devon League runners-up will run out at Twickenham on Sunday in the RFU Senior Vase final (1pm).
They will take on Yorkshire side and previous finalists Wath-upon-Dearne at the home of English rugby.
It is the first time Saltash have played at Twickenham in their 49-year history.
Club president Bill Ryan, who helped found the club in 1969, admits it is going to be a special day.
“As you can imagine the excitement is building as the day approaches,” said Ryan.
“The air of disbelief has vanished and reality has kicked in about what we have ahead of us.
“But it will be very exciting. There’s huge excitement in the town and from all corners of the globe really. We’ve got people coming from Dubai, a group of lads have cut short their stag weekend in Portugal to be there and a lot of fonder members are regrouping to be there.
“We have got five coach loads of supporters going up and that’s not including the players coach.
“The players and officials are going up on Saturday and stopping at Slough.
“Slough Rugby Club have kindly offered their facilities to us and we shall be having an evening dinner there.”
“There were obviously no hard feelings as they were one of the first clubs to offer their services,” said Ryan. “Others did as well. Farnham, who beat us last year in the semi-finals, and Twickenham also offered their facilities to us.”
When asked if it really was the biggest day in the club’s history, Ryan said: “Oh yeah absolutely, by a Cornish mile!”
He added: “I would like to think that when our boys get on the pitch they will treat it like a normal game, but I can’t see that happening. I’m sure it will get to them at some point, whether it’s in the tunnel, on the coach, the walk to the dressing rooms, or when walking on to the pitch – there’s just so much history there. For them it is the game of their lives, whether they win or lose.
“But we are going to enjoy ourselves. If we win that would be the cream on the top of the cup cake. Let’s hope we do emerge as winners, but it is about the occasion. It is going to be a good day.”
Prior to Saltash’s game, Devon One side South Molton will play Old Otlensians (11am), while at 5pm Cornwall will take on Yorkshire in the Under-20 County Championship final.
All the matches will be shown live on Sky Free Sports (Channel 422 or 424), FreeSat (252) and Freeview (Channel 95) and also streamed on the RFU website.
Saltash’s final means star players Will Morton and Lewis Wells are set to miss out on the chance to play for Cornwall in their opening County Championship match against Surrey at Redruth on Saturday.
Cornwall, coached by former Plymouth Albion boss Graham Dawe, have reached the final for the last five seasons, but have a much-changed and less experienced squad this year.
They have lost the services of star players from last season Sam Matavesi and Robin Wedlake, who have moved to the Cornish Pirates, and will not have Matt Shepherd or any other contracted Plymouth Albion players available until their final match due to rearranged league games.
But the Duchy are hoping some of their younger and lower league players will step up.
“We are looking forward to another County Championship campaign,” said Dawe. “We know there is always pressure.
“Wearing the Cornwall shirt brings responsibility and I’m sure everyone will give 100 per cent.
“We had a very competitive fixture with Surrey up there at the start of last year’s campaign and we are in exactly the same situation with them first again. That first game is always about trying to find your feet.”
Devon are also at home on the opening weekend of the County Championship. They entertain Gloucestershire at Brixham (2.30pm). Seven Ivybridge and two Plymstock Albion Oaks players are in the Devon squad. Full preview of that match can be found HERE.
Meanwhile, Tavistock will travel to Wessex on Saturday in a rearranged Cornwall/Devon League match.
Wessex will be relegated no matter what happens, while Tavistock are safe but need a win to guarantee 10th spot.
Coach Hammy Kerswill said: “We are looking forward to signing our season off. It’s been a long and unusual season for us but hopefully we can end it on a high.
“Will Reed will undertake his last ever game coaching, so I hope we can send him off on a high and end the season on a good note.”
Elsewhere, Devonport Services Rhys Williams will start for the Navy in their big match against the Army at Twickneham on Saturday (3pm).
Also in the Navy starting line-up is Albion’s Seti Raumakita and former Plymouth players Matavesi, Jarrad Hayler, Gareth Evans.