A proof may be given along the lines of the proof of the Jordan Curve theorem by Doyle (see this answer). This uses the fundamental group and a variation on Van Kampen, but not homology. So this probably still won't be satisfying to you, but it doesn't use Alexander duality (which is the normal way to do this).
By removing a point from the knot, we may assume that we have a properly embedded line $L\subset \mathbb{R}^3$. Suppose that $\mathbb{R}^3-L$ is disconnected. Since $L$ is closed, $\mathbb{R}^3-L$ is open, and since it is disconnected, there are disjoint non-empty open subsets $U, V$ such that $U\cup V=\mathbb{R}^3-L$. Now embed $\mathbb{R}^3\subset \mathbb{R}^4$, with coordinates $(x,y,z,w)$, and $w=0$ gives $\mathbb{R}^3$. Then $\pi_1(\mathbb{R}^4-L)$ is non-trivial. This requires a generalization of Van Kampen's theorem which one can find, for example, in Peter May's book, Chapter 2.
One may write $\mathbb{R}^4-L$ as a union of two simply connected open sets whose intersection is disconnected. These are $\{w>0\}\cup (\mathbb{R}^3-L) \times (-1,1)$ and $\{w<0\}\cup (\mathbb{R}^3-L) \times (-1,1)$. The intersection is $(\mathbb{R}^3-L) \times (-1,1)$, which is disconnected.
Then the generalized Van Kampen's theorem implies $\pi_1(\mathbb{R}^4-L) \neq 0$. However, just as in Doyle's proof of the Jordan curve theorem, one may find a homeomorphism of $\mathbb{R}^4$ sending $L$ to the $w$-axis, whose complement is simply-connected (move L to its graph by a homeomorphism using the Tietze extension theorem, then project it to the $w$-axis; this has the same proof as Lemma 5.22 in Armstrong's book). This is a contradiction.
**Remark: ** One could use homology instead of fundamental group to carry out this argument, with Mayer-Vietoris replacing generalized Van Kampen.