The month-long Lifeline Expedition from Hull to London has been organised to apologise for the slavery, the BBC reports.
Lady Kate Davson, a descendant of anti-slavery campaigner William Wilberforce, will join the 30-strong group for the first two days.
Deputy Prime Minister John Prescott is also expected to join the march before it reaches Westminster on 25 March.
The Bishop of Hull opened the expedition on Thursday morning by anointing the marchers with water from the font where William Wilberforce, who was elected as MP for the city in 1780, was baptised.
Those joining the walk include people whose ancestors were slaves or employed slaves.
Organiser David Pott said they hoped the walk would also draw attention to the estimated 12 million people the International Labour Organisation reports are working in modern slavery.
He said: "I have been reminded that it is normal that expeditions involve risks - slave trading expeditions were risky ventures.
"So as we seek to undo the damage initiated by the slave trade it should be no surprise that we face challenges. However, on our journey we will not suffer a fraction of what slaves went through."
He added that other people were welcome to join the march at any point during the event.
