The trip will provide the couple with an opportunity to showcase causes they're heavily involved with as well as develop and deepen various existing ties between the UK and Africa.
Here are a few moments to watch out for in the coming days:
1. Waiting for Archie
Only a few images have been shared of baby Archie so far, but we are expecting him to appear at his first official engagement while in South Africa.
When and where will depend on how he's feeling and whether his parents feel he's ready.
When he does appear, cue a collective: "Hasn't he grown!" followed by extended deliberations over whether he takes after his mother or his father.
2. All eyes on the Duchess
Royal tours are carefully orchestrated affairs and this one has been arranged so Harry and Meghan aren't attending lots of separate events at the same time. By doing so, we -- the media -- can focus on one theme at a time.
Meghan's program has her stamp all over it. With a clear focus on promoting women's education, health, entrepreneurship and leadership -- it's very much a continuation of what we've already seen with her cookbook and clothing collaboration.
We still don't know how much of Meghan we will see in South Africa while Prince Harry travels on to Botswana, Angola and Malawi. She's never been to South Africa before but she will also, no doubt, be aware that everything she does on a high-profile visit like this will speak to her royal brand. Commentators will pore over how she's putting herself across and -- yes -- what she wears.
3. The couple's passions
Royals express what they are passionate about through the causes they choose to support, and the way they throw themselves into relevant engagements.
We learn a little more about the couple each time we see them, and we'll be looking out for any comments they make along the way. What they choose to emphasize will indicate how they plan to carry their public roles forward.
4. Honoring Diana
Harry has deliberately picked up much of his mother's work, to continue her legacy, most notably in relation to land mine clearance and HIV-AIDS awareness.
As Harry retraces his mother's steps in Angola for example, it will become apparent how pioneering she was for her era and we will see a stark illustration of progress since her death.
5. Other family links
Harry's father, Prince Charles, and grandfather, Prince Philip, were ahead of their time on conservation issues, and that will also be reflected during the tour.
The royal family is deeply rooted in the continent. Princess Elizabeth's defining 21st birthday speech was delivered from Cape Town, South Africa, where the Sussexes' tour begins and she was in Kenya when she found out that her father had died and she had become Queen.
It's going to be mayhem, but everyone knows that, so let's see how it's managed.
To say this is going to be a "high-profile tour" would be an understatement. The royal press pack is operating at full capacity with teams flocking in from London and local media have been rushing to accredit too.
The tricky thing to get right for the organizers is how to allow the couple the freedom to engage with people while keeping everyone safe.
Lessons will certainly have been taken from the couple's Commonwealth tour last fall, when they visited Australia, New Zealand, Tonga and Fiji. During the Fiji leg, a walkabout at an open-air market had to be cut short over the excessive numbers that had turned out to see Meghan.
This time around, measures are already being taken with some details of the couple's itinerary like the township engagement location embargoed until shortly before they arrive. It is also unknown where exactly the family will stay throughout their trip -- though it is assumed that, where possible, they will likely stay at official residences and properties selected by the UK Foreign and Commonwealth office.
7. The public reaction
Senior royals always get a good turnout but this couple have the youth and celebrity factors thrown in. This arguably makes them the most high-profile couple in the world right now.
So, how large will the crowds be? What is it they like about the couple? How will social media react? Will race yet again emerge as an issue as it often does for the Duchess? We'll soon find out.
8. The unexpected
There's only so much you can expect from a royal tour though, because the biggest moments are often the unexpected ones.
Perhaps an image, a moment or a cursory word that somehow will resonate further afield, and speaks to the couple somehow. With 10 days, four countries and more than 30 engagements ahead of us, who knows when it will come?