Whether you're using a knife, a meat slicer, or a tool specifically designed to slice your beef jerky, slicing in the wrong direction with any of these instruments will result in a chewy piece of beef jerky.
The general advice is to slice the meat both thin (1/8 - 1/4" thick) and against the grain.
With that said, some folks do prefer their jerky somewhat "chewy." If this is you, I'd suggest slicing thin, and with the grain.
To start, you'll need a few things to slice jerky. I slice my jerky in one of two ways:
I know there are specific tools designed to slice strips of beef jerky into uniform pieces but in my opinion, you'll find more utility in a meat slicer. I use mine to slice jerky, deli meat, bacon, etc.
For the sake of this article I used my knife because I realize people new to jerky likely don't own a slicer; For folks with a slicer, a picture is provided below.
To slice beef jerky, you'll need:
1. For starters, if you bought the meat refrigerated, you should pop it into the freezer for 30 minutes to an hour. The reason for doing this is because it makes the meat much easier to slice - especially when using a knife.
Conversely, if you bought the meat frozen, allow it to thaw until it's somewhat malleable. Again, you don't want the meat to be entirely thawed.
2. Identify if the meat has a fat cap or exterior silver skin and remove it.
Here's a london broil after removing silverskin and exterior fat:
Here's another example of eye of round trimmed:
Eye of round typically has an exterior fat cap that butchers leave on since the cut is usually designed for roasts.
Fat is removed because it provides no benefit for jerky as it won't render and will go rancid - especially over time. This is also why you should start with a lean cut of meat - like those from the Rump of the steer.
Similarly, silver skin will not render as it's a protein elastin. Rather, it will twist and bend and will result in a chewy mouth-feel which isn't appetizing. You can learn more about silverskin in this article.
When slicing thick silver skin, angle your knife up towards the silverskin. With your other hand, support the silverskin as you remove it, this way you maximize your jerky yield.
Once the meat is void of fat and silverskin, you can begin making your slices.
3. The first thing to look for when making your slices is the grain direction of the meat - this is the direction the protein fibers run.
Put simply: The orientation of the "lines" on the lean meat.
To illustrate, here's an example with the london broil above:
To further illustrate, I cut the roast in half and the dotted line is how I'd slice:
The cut to the left would be against the grain, while the cut on the right would be with the grain (I rotated the halved piece 90 degrees counter-clockwise).
The general advice is to slice the meat against this grain structure - the reason for this is because you're shortening the fiber lengths, which makes it easies for your teeth to separate.
In terms of thickness for the jerky, you want to be around 1/8 - 1/4" thick on all pieces. This way the jerky slices dehydrate at around the same time.
With all that said, I do know lots of people who enjoy chewy jerky that has more of a "bite." It really boils down to personal preference.
To summarize your options for slicing jerky:
Align those outcomes with your preference and slice accordingly.
If this is your first time making jerky, I'd do a majority of it against the grain and then maybe 1-2 pieces with the grain; Try both and see what you prefer.
The advice here isn't much different than slicing with a knife. You still want your jerky somewhat frozen so that the slicer can make cleaner slices.
Quick Tip: If your slicer blade is removable and not too cumbersome, I'd suggest popping it into your freezer for 30 minutes. This way there is less thermal difference between the surface of the blade and the meat.
I do this same thing with my meat grinder attachment when I make ground beef.
To illustrate, I used a frozen eye of round which I know the general grain direction of.
If you were to slice this eye of round with the grain, you'd place your meat on your slicer like this:
If you're slicing against the grain, you'd put your meat on the slicer like this:
That's all there is to slicing meat for jerky.
Simply identify the grain and slice the meat into strips that are roughly 1/4-1/8" thick.