We study the model operator $\mathbf{D}_{\mathbf{A}} = (d/dt) + \mathbf{A}$ in $L^2(\mathbb{R};\mathcal{H})$ associated with the operator path $\{A(t)\}_{t=-\infty}^{\infty}$, where $(\mathbf{A} f)(t) = A(t) f(t)$ for a.e.\ $t\in\mathbb{R}$, and appropriate $f \in L^2(\mathbb{R};\mathcal{H})$ (with $\mathcal{H}$ a separable, complex Hilbert space). Denoting by $A_{\pm}$ the norm resolvent limits of $A(t)$ as $t \to \pm \infty$, our setup permits $A(t)$ in $\mathcal{H}$ to be an unbounded, relatively trace class perturbation of the unbounded self-adjoint operator $A_-$, and no discrete spectrum assumptions are made on $A_{\pm}$. We introduce resolvent and semigroup regularized Witten indices of $\mathbf{D}_{\mathbf{A}}$, denoted by $W_r$ and $W_s$, and prove that these regularized indices coincide with the Fredholm index of $\mathbf{D}_{\mathbf{A}}$ whenever the latter is Fredholm. In situations where $\mathbf{D}_{\mathbf{A}}$ ceases to be a Fredholm operator in $L^2(\mathbb{R};\mathcal{H})$ we compute its resolvent (resp., semigroup) regularized Witten index in terms of the spectral shift function $\xi(\,\cdot\,;A_+,A_-)$ associated with the pair $(A_+, A_-)$ as follows: Assuming $0$ to be a right and a left Lebesgue point of $\xi(\,\cdot\,\, ; A_+, A_-)$, denoted by $\xi_L(0_+; A_+,A_-)$ and $\xi_L(0_-; A_+, A_-)$, we prove that $0$ is also a right Lebesgue point of $\xi(\,\cdot\,\, ; \mathbf{H_2}, \mathbf{H_1})$, denoted by $\xi_L(0_+; \mathbf{H_2}, \mathbf{H_1})$, and that \begin{align*} W_r(\mathbf{D}_{\mathbf{A}}) &= W_s(\mathbf{D}_{\mathbf{A}}) \\ & = \xi_L(0_+; \mathbf{H_2}, \mathbf{H_1}) \\ & = [\xi_L(0_+; A_+,A_-) + \xi_L(0_-; A_+, A_-)]/2, \end{align*} the principal result of this paper. In the special case where $\dim(\mathcal{H}) < \infty$, we prove that the Witten indices of $\mathbf{D}_{\mathbf{A}}$ are either integer, or half-integer-valued.